Abstract: Objective To explore the gene expression characteristics and prognostic markers of canine spontaneous breast cancer. Method Multiple canine breast cancer transcriptome datasets were obtained from public databases and corrected and merged to obtain an integrated dataset with large sample size. By bioinformatics analysis, genes related to disease prognosis were clustered. The key characteristic genes that were related to poor prognosis were screened and then verified by cell proliferation assays. Result Cluster 3 obtained by consensus clustering analysis was associated with a low survival rate of the dogs with breast cancer. The characteristic genes in cluster 3 were mainly enriched in cell proliferation-related signaling pathways. By univariate analysis followed by extracting the intersection genes with the human database, 11 cross-species conserved key genes related to poor prognosis of breast cancer were obtained. Two of these conserved genes, ZBTB16 and ABI3BP, were confirmed to be participate in regulating the proliferation of canine breast cancer cells. Conclusion A series of conserved risk genes was obtained. This key gene cluster could be used as biomarkers for disease classification and prognosis evaluation of canine spontaneous breast cancer, as well as the canine breast cancer animal models.

Key words: breast cancer, dogs, animal model, biomarkers, risk genes, prognosis

摘要： 目的 探索犬自发性乳腺癌的基因表达特征和预后标志物。 方法 从公共数据库获取多个犬乳腺癌转录组数据集,校正合并获得大样本量的整合数据集。 通过生物信息学分析与疾病预后相关的基因聚类,筛选与预后不良相关的特征性基因并在细胞水平进行验证。 结果 共识聚类分析获得的聚类 3 与犬乳腺癌的低生存率相关,其特征性基因主要富集于细胞增殖相关信号通路。 经过单因素分析并与人类数据集提取交集基因,获得 11 个与乳腺癌预后不良相关的跨物种保守性关键基因。 利用犬乳腺癌细胞系证实其中的 ZBTB16 和 ABI3BP 基因参与调节乳腺癌细胞增殖。 结论 成功获得一组保守性风险基因,可作为生物标志物用于犬自发性乳腺癌及犬乳腺癌动物模型的疾病分型和预后评估。

关键词: 乳腺癌, 犬, 动物模型, 生物标志物, 风险基因, 预后